The primary etiologic factors leading to the sporadic (non-familial) form of the lethal neurodegenerative disease amyotrophic lateral sclerosis (ALS) remain unknown. The National ALS Registry collects information on environmental risk factors from patients who register through the on-line portal. However, it is not known how representative the risk factor data in the National ALS Registry are in comparison with the population of ALS patients as a whole. We will develop a surveillance program that will achieve complete ascertainment of ALS cases in Northern / Central Ohio (Specific Aim 1). We will conduct a population case control study of risk factors for ALS based on data collected with a specially designed environmental questionnaire from the patients collected in the Ohio surveillance program and randomly selected population control subjects from the same region (Specific Aim 2). We will compare ALS patients to random controls with regard to levels of exposure to the cyanobacterial neurotoxin, ?-N-methylamino-L-alanine (BMAA), and other environmental toxicants, including lead, mercury and pesticides, as potential risk factors for sporadic ALS. The central hypothesis is that the risk of developing ALS increases with dose and duration of exposure to these risk factors in susceptible individuals. Exposures will be determined by: (i) history of exposure to cyanobacteria and involvement in at-risk occupations, using questionnaire data; (ii) dietary intake of mercury, using questionnaire data on fish consumption and databases of methylmercury in fish; and (iii) the geospatial distribution of residential exposure to environmental toxins/toxicants. Mapping of at-risk exposures will include: (i) lifetime residential histories; (ii) sources of potential environmental toxicants (Brownfield ad Superfund sites, hazardous waste sites, agricultural pesticides) and cyanobacteria in waterbodies (Specific Aim 3). The geographical mapping program will be a case control study of exposures in Ohio ALS surveillance program patients and random controls from the general population. The content of cyanobacteria in waterbodies throughout Northern / Central Ohio will be determined using a combination of direct sampling and aerosol collections from waterbodies, and calibrated satellite remote sensing. Our approach is innovative; it is the first comprehensive ALS surveillance program in Ohio, a state with many hazardous waste sites that also borders Lake Erie, which has massive cyanobacterial blooms; it is the first in-depth analysis of exposure to cyanobacteria as a risk factor for ALS in Ohio; and it is the first comprehensive analysis of th relative risks of the full range of incriminated environmental risk factors for ALS using geospatia mapping. Identifying the specific environmental toxins/toxicants that increase risk of ALS will enable exposure reduction initiatives to prevent this debilitating and lethal disease.